Project Summary: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect. The vast majority of survivors of corrective TOF surgery will be left with some degree of pulmonary regurgitation (PR). TOF patients with significant PR are known to develop right ventricular (RV) enlargement and right heart failure, ventricular arrhythmia, sudden death, and decreased exercise performance over time. Nearly all studies in this regard are retrospective with much less data in pediatric TOF than adults. Multiple studies in adults TOF survivors have suggested that pulmonary valve replacement (PVR) may alleviate many of the clinical symptoms and allow the RV to remodel; furthermore, numerous studies have suggested that PVR in the asymptomatic patients may prevent clinical decline. The timing of PVR in the asymptomatic TOF patient is crucial, especially in light of the knowledge that prosthetic valve integrity is limited. Despite the lack of robust prospective evidence, PVR is nevertheless occurring in adolescent TOF patients. With the advent of transcatheter PVR, an increasing number of patients will undergo this procedure, making knowledge of the benefits and timing of the procedure, which have generally been based on cardiac magnetic resonance (CMR) derived RV volumes mostly in adults, even more critical. Retrospective studies have varied regarding the optimal threshold values for PVR; the practice of when and even if PVR should be performed varies widely between institutions and even within practice groups. To guide clinicians, a randomized, prospective trial is needed to determine if PVR in adolescents is beneficial both in the short and long terms. We propose to perform such a trial in a multicenter fashion, creating a structured framework upon which a future, large scale trial can be built. To design such a trial, we propose a feasibility protocol to obtain pilot data including parameters such as the number of patients to screen, acceptance of a randomized trial of PVR, comparisons between PVR and those who do not undergo PVR after 1-1.5 years in quality of life (QOL), exercise testing and Holter monitoring, which will inform the endpoints for the larger, longer term trial. This feasibility protocol will also use innovative CMR techniques to determine the mechanism of clinical outcome in this patient population. The objectives of this application are: 1) To determine the operational feasibility of performing a randomized multi-center trial, 2) To measure clinical parameters needed to design a large scale clinical trial by performing a short term pilot protocol and 3) To determine mechanisms of the effects of PVR in the definitive trial by obtaining preliminary data using innovative techniques such as diffuse fibrosis (DF), performing exercise CMR and measuring biventricular strain. Our hypotheses is that a randomized, multicenter, prospective clinical trial of PVR in TOF survivors is feasible, that clinical metrics exist to inform a large longer term clinical trial to discern who would benefit and optimize timing of the procedure and that PVR in asymptomatic TOF survivors will demonstrate improved exercise, strain, QOL and less DF.